PMID- 34099720
OWN - NLM
STAT- MEDLINE
DCOM- 20210622
LR  - 20240402
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Jun 7
TI  - Deep learning boosts sensitivity of mass spectrometry-based immunopeptidomics.
PG  - 3346
LID - 10.1038/s41467-021-23713-9 [doi]
LID - 3346
AB  - Characterizing the human leukocyte antigen (HLA) bound ligandome by mass 
      spectrometry (MS) holds great promise for developing vaccines and drugs for 
      immune-oncology. Still, the identification of non-tryptic peptides presents 
      substantial computational challenges. To address these, we synthesized and 
      analyzed >300,000 peptides by multi-modal LC-MS/MS within the ProteomeTools 
      project representing HLA class I & II ligands and products of the proteases AspN 
      and LysN. The resulting data enabled training of a single model using the deep 
      learning framework Prosit, allowing the accurate prediction of fragment ion 
      spectra for tryptic and non-tryptic peptides. Applying Prosit demonstrates that 
      the identification of HLA peptides can be improved up to 7-fold, that 87% of the 
      proposed proteasomally spliced HLA peptides may be incorrect and that dozens of 
      additional immunogenic neo-epitopes can be identified from patient tumors in 
      published data. Together, the provided peptides, spectra and computational tools 
      substantially expand the analytical depth of immunopeptidomics workflows.
FAU - Wilhelm, Mathias
AU  - Wilhelm M
AUID- ORCID: 0000-0002-9224-3258
AD  - Computational Mass Spectrometry, Technical University of Munich (TUM), Freising, 
      Germany. mathias.wilhelm@tum.de.
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany. mathias.wilhelm@tum.de.
FAU - Zolg, Daniel P
AU  - Zolg DP
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany.
FAU - Graber, Michael
AU  - Graber M
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany.
FAU - Gessulat, Siegfried
AU  - Gessulat S
AUID- ORCID: 0000-0001-5530-0674
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany.
FAU - Schmidt, Tobias
AU  - Schmidt T
AUID- ORCID: 0000-0002-1883-6514
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany.
FAU - Schnatbaum, Karsten
AU  - Schnatbaum K
AD  - JPT Peptide Technologies GmbH, Berlin, Germany.
FAU - Schwencke-Westphal, Celina
AU  - Schwencke-Westphal C
AUID- ORCID: 0000-0002-5105-4290
AD  - Klinik und Poliklinik fur Innere Medizin III, Klinikum rechts der Isar, School of 
      Medicine, Technical University of Munich (TUM), Munich, Germany.
AD  - German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
AD  - Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
FAU - Seifert, Philipp
AU  - Seifert P
AD  - Klinik und Poliklinik fur Innere Medizin III, Klinikum rechts der Isar, School of 
      Medicine, Technical University of Munich (TUM), Munich, Germany.
AD  - Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
FAU - de Andrade Kratzig, Niklas
AU  - de Andrade Kratzig N
AD  - Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
AD  - Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
AD  - Klinik und Poliklinik fur Innere Medizin II, Klinikum rechts der Isar, School of 
      Medicine, Technical University of Munich (TUM), Munich, Germany.
FAU - Zerweck, Johannes
AU  - Zerweck J
AD  - JPT Peptide Technologies GmbH, Berlin, Germany.
FAU - Knaute, Tobias
AU  - Knaute T
AD  - JPT Peptide Technologies GmbH, Berlin, Germany.
FAU - Braunlein, Eva
AU  - Braunlein E
AD  - Klinik und Poliklinik fur Innere Medizin III, Klinikum rechts der Isar, School of 
      Medicine, Technical University of Munich (TUM), Munich, Germany.
AD  - Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
FAU - Samaras, Patroklos
AU  - Samaras P
AUID- ORCID: 0000-0001-6042-1585
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany.
FAU - Lautenbacher, Ludwig
AU  - Lautenbacher L
AUID- ORCID: 0000-0002-1540-5911
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany.
FAU - Klaeger, Susan
AU  - Klaeger S
AUID- ORCID: 0000-0002-0074-5163
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Wenschuh, Holger
AU  - Wenschuh H
AD  - JPT Peptide Technologies GmbH, Berlin, Germany.
FAU - Rad, Roland
AU  - Rad R
AUID- ORCID: 0000-0002-6849-9659
AD  - Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
AD  - Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
AD  - Klinik und Poliklinik fur Innere Medizin II, Klinikum rechts der Isar, School of 
      Medicine, Technical University of Munich (TUM), Munich, Germany.
FAU - Delanghe, Bernard
AU  - Delanghe B
AD  - Thermo Fisher Scientific, Bremen, Germany.
FAU - Huhmer, Andreas
AU  - Huhmer A
AD  - Thermo Fisher Scientific, San Jose, CA, USA.
FAU - Carr, Steven A
AU  - Carr SA
AUID- ORCID: 0000-0002-7203-4299
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Clauser, Karl R
AU  - Clauser KR
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Krackhardt, Angela M
AU  - Krackhardt AM
AUID- ORCID: 0000-0002-4752-0543
AD  - Klinik und Poliklinik fur Innere Medizin III, Klinikum rechts der Isar, School of 
      Medicine, Technical University of Munich (TUM), Munich, Germany.
AD  - German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
AD  - Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, 
      Technical University of Munich (TUM), Munich, Germany.
FAU - Reimer, Ulf
AU  - Reimer U
AD  - JPT Peptide Technologies GmbH, Berlin, Germany.
FAU - Kuster, Bernhard
AU  - Kuster B
AUID- ORCID: 0000-0002-9094-1677
AD  - Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), 
      Freising, Germany. kuster@tum.de.
AD  - Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), Technical University 
      of Munich (TUM), Freising, Germany. kuster@tum.de.
LA  - eng
GR  - U01 CA214125/CA/NCI NIH HHS/United States
GR  - U24 CA210986/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210607
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (ASPN protein, human)
RN  - 0 (Epitopes)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
SB  - IM
EIN - Nat Commun. 2021 Jun 23;12(1):4002. PMID: 34162890
MH  - Cell Line
MH  - *Deep Learning
MH  - Epitopes
MH  - Extracellular Matrix Proteins/metabolism
MH  - HLA Antigens/immunology
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Humans
MH  - Ligands
MH  - Mass Spectrometry
MH  - Molecular Medicine
MH  - Peptides/*immunology/metabolism
MH  - Proteomics
MH  - Tandem Mass Spectrometry/*methods
PMC - PMC8184761
COIS- D.P.Z., S.G., T.S., M.W., and B.K. are founders and shareholders of MSAID GmbH. 
      M.W. and B.K. are also founders and shareholders of OmicScouts GmbH, they have no 
      operational role in both companies. K.S., J.Z., T.K., and U.R. are employees of 
      JPT Peptide Technologies. B.D. and A.H. are employees of Thermo Fisher 
      Scientific. During the study, S.G. was an employee of SAP SE. S.A.C. is a member 
      of the scientific advisory boards of Kymera, PTM BioLabs, Seer and BioAnalytix 
      and a scientific advisor to Pfizer and Biogen.
EDAT- 2021/06/09 06:00
MHDA- 2021/06/23 06:00
PMCR- 2021/06/07
CRDT- 2021/06/08 06:11
PHST- 2020/11/10 00:00 [received]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/06/08 06:11 [entrez]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2021/06/23 06:00 [medline]
PHST- 2021/06/07 00:00 [pmc-release]
AID - 10.1038/s41467-021-23713-9 [pii]
AID - 23713 [pii]
AID - 10.1038/s41467-021-23713-9 [doi]
PST - epublish
SO  - Nat Commun. 2021 Jun 7;12(1):3346. doi: 10.1038/s41467-021-23713-9.